Medical 'smart bomb' key to eradicating cancer cells

A medical ‘smart bomb’ designed to seek out and eradicate the root of cancer cells is being developed by Deakin University medical researchers.

In collaboration with scientists in India and Australia, the Deakin researchers are working on a new generation of cancer medications that would target and kill cancer-initiating cells and would be more effective and cause fewer side-effects in patients than current treatments.

“Our aim is to develop a safe and novel drug delivery system that hits the cancer at its core and kills the cells responsible for the resistance to current therapies and the recurrence of the disease,” said Associate Professor Wei Duan, the project leader and researcher with Deakin’s Medical School.

“The success of this project will bring us a step forward in significantly improving the survival rate and quality of life of cancer patients. Our precision-guided cancer therapy will afford reduced side-effects, decreased toxicity to normal cells and increased treatment effectiveness.

It also has potential for the treatment of neurodegenerative diseases, such as Alzheimer’s Disease, heart disease and diabetes.”

The project is a collaboration between Deakin University’s School of Medicine, the Institute for Technology Research and Innovation and the Indian Institute of Science in Bangalore along with Barwon Health’s Andrew Love Cancer Centre and ChemGenex Pharmaceuticals. It has received $400,000 funding over three years from the Federal Government’s Australia-India Strategic Research Fund, with reciprocal support from the Indian Government.

The molecular ‘smart bomb’ being developed by the researchers would safely deliver drugs through the body, seeking out and penetrating a cancer cell before releasing the anti-cancer drugs within the cell, killing the cancer cell.

“Cancer cells are particularly difficult to kill as they contain so-called cancer stem cells, the root or seed cancer cells that are resistant to drugs,” Associate Professor Duan explained.

“While current treatments kill the bulk of the cancer cell, the cancer root escapes the therapy and can regenerate into a new cancer mass.

“The aim of our research is to develop a ‘smart bomb’ that can penetrate the cell and release the drugs within the cells, rather than from the outside, and kill the whole tumour, root and all.

“This system would also be very human compatible and human degradable meaning it would not be toxic to other cells in the body and would cause very limited side-effects.”

The researchers are building on a technique known as RNA interference, or gene silencing, which enables control over the genes inside cells. This technique will be combined with a cancer targeting aptamer – a molecular guided missile that is designed to bind to other cells. The result will be a molecular ‘smart bomb’ that safely delivers drugs through the body, seeking out and penetrating a cancer cell before releasing the anti-cancer drugs within the cell, killing the whole tumour.

Cancer cells are made up of many cells that have different characteristics. They are, for example, like a tree with some cells being the root system and the others the branches and leaves; if you cut off the branches and leaves, the root of the tree is still alive.

Current cancer treatments are ineffective in eradicating the whole cancer cell because they only kill the branches and leaves. The root cells are particularly tough and resistant to drugs. They possess drug pumps that pump out the anti-cancer drugs. This means that, while most of the cancer cell is killed, the cancer root remains and can regenerate. This makes the root cells (cancer stem cells) an important target for new cancer treatments.

There are two parts to the project being undertaken by the Deakin and Indian scientists.

The first is building the guided missile, or aptamer. The aptamer is a chemical antibody, much smaller and cheaper and easier to make than conventional antibodies, designed to bind specifically to cancer cells. It will be designed to effectively penetrate a tumour and specifically target cancer stem cells. This missile will carry the ‘bomb’; the second part of the drug delivery system.

The ‘bomb’ will be a very smart lipid particle that will remain stable in the body, i.e. it will not break down. This particle will carry the anti-cancer drug as well as anti-cancer genes.

When combined, the ‘smart bomb’ will be injected into the body and find the cancer cell. It will then enter the cell through an endosome route – a small road within the cell. Once inside the cell, it will very quickly release its contents and kill the whole cancer cell.

A unique part of the system being developed is that the bomb is very stable outside the cancer cell, but once inside it will very quickly release its contents and kill the cancer cell from within. This system is made by materials that are very human compatible and human degradable – it is not toxic to other cells in the body and would cause very limited side-effects.